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April 1, 2013 Volume 77, Number 4
Trauma-Induced Coagulopathy and Role of a Massive Transfusion Protocol in Trauma Anesthesia Charles E. Smith, M.D.

The treatment of shock after trauma requires a systematic approach to rapidly and accurately diagnose injuries and institute therapy. Definitive control of hemorrhage is essential, together with restoration of adequate circulating blood volume. Use of a massive transfusion protocol (MTP) facilitates rapid availability of components in an increased ratio of plasma and platelets to packed red blood cells (RBCs). The PROPPR study (Pragmatic Randomized Optimal Platelet and Plasma Ratios) is investigating 1:1:1 versus 1:1:2 ratios of Plasma:Platelet:RBC products given to trauma patients who are predicted to require massive transfusions Point-of-care viscoelastic assays may allow for goal-directed therapy in trauma-induced coagulopathy (TIC) and massive transfusion, including the use of antifibrinolytics when appropriate. Unresolved issues remain, including use of fibrinogen and/or prothrombin complex concentrate, MTP use in blunt versus penetrating trauma, optimal transfusion ratios, and timing of blood component administration. Understanding the mechanism of hemorrhage is clearly required in order to provide optimal treatment. The Trans-Agency Research Consortium for Trauma-Induced Coagulopathy (TACTIC) may help in this regard Further information regard-ing MTP, plasma, platelets, additional plasma derivatives and RBC transfusion is available from the ASA Committee on Blood Management

Trauma-Induced Coagulopathy
TIC patients may have a complex coagulation disorder involving dilution of pro-coagulant, anti-coagulant, pro-fibrinolytic and anti-fibrinolytic factors. TIC is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. It appears to be due to activation of anticoagulant and fibrinolytic pathways, although the exact mechanism is not known. The thrombomodulin-protein C pathway has been implicated, with shock and hypoperfusion playing key roles. Hyperfibrinolytic states may be seen in up to 20 percent of trauma patients. Fibrinolysis is increased due to dilution of FXIII and α2-antiplasmin, which reduces fibrin cross-linking, decreases resistance to fibrinolysis and prolongs plasmin half-life. Plasminogen activator inhibitor is decreased, prolonging tissue plasminogen activator (tPA) activity. Excessive fibrinolysis contributes to bleeding and mortality.

In a case-control study of trauma patients with and without TIC (defined as elevated prothrombin time), patients with TIC had decreased common and extrinsic pathway factor activities (factors V and VII) and decreased inhibition of the coagulation cascade (antithrombin and protein C activities) compared to matched control patients without TIC. Both cohorts had evidence of increased prothrombin fragment 1.2 levels, thrombin-antithrombin complexes, soluble fibrin monomer, d-dimer levels and plasminogen activator inhibitor-1 activity above normal reference values.

Role of a Massive Transfusion Protocol
An MTP is activated in response to a patient experiencing severe bleeding (Table 1). In addition to the MTP, efforts are directed toward hemostatic resuscitation, including control of surgical bleeding, correction of hypothermia, acidosis, shock, and coagulopathy and limiting the use of isotonic crystalloids. Hypotensive resuscitation (systolic blood pressure 80-100 mmHg) is generally preferred until hemorrhage is controlled (unless there is concern for brain and/or spinal cord injury). Fibrinogen levels above 150 mg/dL are targeted.

A commonly used definition of massive transfusion in the adult trauma setting is >10 units RBCs in 24 hours. A more practical means for activating the MTP is requirement for >4 RBC units in one hour with ongoing need for transfusion, or blood loss >150 ml/min with hemodynamic instability and need for transfusion. Once the MTP is activated, the blood bank is able to ensure rapid and timely availability of blood components to facilitate hemostatic resuscitation.

Approximately 3-5 percent of civilian adult trauma patients receive massive transfusion. Predictive factors for massive transfusion are penetrating mechanism, positive FAST (focused assessment sonography in trauma), arrival blood pressure <90 mmHg and pulse >120 bpm. Patients receiving uncross-matched red cells in the emergency department are three times more likely to receive massive transfusion. In military trauma, casualties presenting with heart rate >110 bpm, systolic blood pressure < 110 mmHg, base deficit < -6, and hemoglobin < 11 g/dl had a high incidence of massive transfusion.

Transfusion of RBCs, plasma, and platelets in a similar proportion as whole blood minimizes the effects of dilutional coagulopathy and hypovolemia. Retrospective studies show a survival advantage of increased plasma: RBC ratio on mortality in massive transfusion. Other studies show a survival advantage with increased platelets: RBCs. The optimal ratio of plasma: RBCs appears to be in the range 1:2.4 or higher. Ideally, hemostatic-based resuscitation should be comple-mented with point-of-care or other laboratory endpoints to direct therapy (e.g., thromboelastography, rotational thromboelastometry).

Once definitive control of hemorrhage is achieved, a restrictive approach to transfusion is preferred because of the known risks of blood product administration.

1. Frith D, Brohi K. The acute coagulopathy of trauma shock: clinical relevance. Surgeon. 2010;8(3):159-163.
2. Smith CE, Bauer AM, Pivalizza EG, et al.; ASA Committee on Blood Management. Massive transfusion protocol (MTP) for hemorrhagic shock. American Society of Anesthesiologists website. Accessed February 19, 2013.
3. Cotton BA, Reddy N, Hatch QM, et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and improvement in survival in 390 damage control laparotomy patients. Ann Surg. 2011; 254(4):598-605.

Complete references available from the author. The author is grateful to members of the ASA Committee on Blood Management for their input. Individuals interested in trauma anesthesia can join the discussion group of the Trauma Anesthesiology Society (  

Charles E. Smith, M.D. is Professor of Anesthesiology, Case Western Reserve University School of Medicine, and Director, Cardiothoracic and Trauma Anesthesia, MetroHealth Medical Center, Cleveland.

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